The role of the immune system in diabetes mellitus is not well defined. The present proposal describes two macrophage-containing populations which possess an insulin-sensitive immune function and specific receptors for insulin. These two cell populations, one a homogeneous cell line and the other a cell preparation from mouse spleen tissue, will be employed to 1) measure the effect of insulin on several immune functions, 2) determine the mechanisms whereby insulin modulates immune functions, and 3) deduce the relevance of these immune functions in the diabetic state. Insulin receptors and macrophage functions will be evaluated in spleen cells from diabetic animals, in the cultured macrophages during the phases of cell growth and in selected clones of the cultured cells. Insulin receptors will be studied by competitive binding assays among several insulins and insulin analogues. The macrophage functions, to include antibody-dependent cytotoxicity, specific and non-specific phagocytosis, glucose transport and amino acid transport, will be studied in the presence and absence of the same insulins and insulin analogues.